Drug & supplement interaction

Bitter Orange + Codeine, Papaverine

Codeine, Papaverine brand name: Copavin.

Minor Interaction
Medically reviewed by · Updated September 2026
The bottom line Minor

Bitter Orange has a minor interaction with Codeine, Papaverine. Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.

Read the full interaction report
SeverityMinor
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Bitter Orange and Codeine, Papaverine

Here is the interaction we found between these two, with the evidence behind it.

Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Codeine, Papaverine

Codeine, Papaverine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Bitter Orange interacts with.

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.
Severity Minor Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the wrinkle with this pairing. Codeine is what we call a prodrug, meaning your body has to switch it on using a liver enzyme called CYP2D6 to turn it into morphine, which is what actually relieves pain and quiets a cough. Bitter orange contains a compound (octopamine) that may very weakly slow that same enzyme down. In theory, that could mean a bit less of your codeine gets converted, so you might feel less pain relief than expected.

Honestly, this one is mostly theoretical. The evidence comes only from lab studies, not real people, and it's rated minor. I wouldn't lose sleep over it. Still, since bitter orange is a stimulant that can bump up your heart rate and blood pressure, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 10 major, 876 moderate, 70 minor known drug interactions in our database — the Codeine, Papaverine one above is one of them. If you take anything else, check it against the full list below.

Major 10 Moderate 876 Minor 70 No known interaction 1,874 (incl. Codeine, Papaverine)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

Covers the 2,830 medications we’ve checked against Bitter Orange. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Codeine, Papaverine

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine, Papaverine page lists 145 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Mistletoe (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 8 major · 114 moderate · 23 minor.

From our pharmacist’s overview on the Codeine, Papaverine page

“Codeine combined with papaverine (Copavin) is an opioid product, and I read its supplement list as one that calls for genuine care. More than half of the 145 entries pile sedation on top of the drug's own, and the standouts are everyday alcohol (beer and wine each carry a major rating, well documented in people) and kava, combinations…”

Reviewed by 2 · Jul 18, 2026

Open the Codeine, Papaverine interaction page

One more smart check

Taking Bitter Orange as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Codeine, Papaverine too, on top of Bitter Orange — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Bitter Orange and Codeine, Papaverine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Bitter Orange
Top 25%

#159 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Codeine, Papaverine
Steady interest

#2,225 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Keep checking

Other Drugs & Bitter Orange

Browse every other medication we’ve checked against Bitter Orange — both the ones with a known interaction and the ones without. Select any drug for the full detail.

10Major
876Moderate
70Minor
1,873No known interaction
10 Major 876 Moderate 70 Minor 1,873 No interaction
Major

10 interactions

Moderate

876 interactions

Showing 60 of 876 moderate interactions — see all 876 on the Bitter Orange page.

Minor

70 interactions

Showing 60 of 70 minor interactions — see all 70 on the Bitter Orange page.

No interaction 1,873 drugs checked — show the list

We also checked Bitter Orange against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,873 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page
See every supplement checked against Codeine, Papaverine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Bitter Orange monograph › Uses, safety, and every drug interaction in one place Codeine, Papaverine supplement interactions › Every supplement checked against Codeine, Papaverine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Bitter Orange and Codeine, Papaverine Together: Common Questions

Can you take Bitter Orange with Codeine, Papaverine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Bitter Orange and Codeine, Papaverine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Codeine, Papaverine and Bitter Orange?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.